Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS)

An Open-Label, Single-Arm Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Early Stage Relapsing Remitting Multiple Sclerosis

This is a prospective, multicenter, open-label, single-arm, phase 3b study which evaluates effectiveness and safety of ocrelizumab in participants with early stage RRMS. The study will consist of an open-label treatment period of 192 weeks and follow-up period of at least 48 weeks.

The optional shorter infusion substudy will evaluate the safety of a shorter infusion of ocrelizumab in a subgroup of participants with early stage RRMS enrolled in the main MA30143 study. Approximately 700 patients will be enrolled in the substudy, and will receive additional 600 mg ocrelizumab administered in a shorter time frame.

Study Overview

• Status: Terminated
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: Ocrelizumab

• Study Type: Interventional
• Enrollment (Actual): 1225
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1437JCP
    • Hospital Churruca Visca
  • Buenos Aires, Argentina, C1424
    • Centro de Especialidades Neurológicas y Rehabilitación - CENyR
  • Rosario, Argentina, S2000BZL
    • Fundacion Rosarina de Neurorehabilitacion
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Brain and Mind Centre
    • Liverpool, New South Wales, Australia, 2170
      • Liverpool Hospital
    • New Lambton, New South Wales, Australia, 2305
      • John Hunter Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital; Department of Neurology
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital; Department of Neurology
    • Heidelberg, Victoria, Australia, 3084
      • Austin Hospital; Department of Neurology
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital; Department of Neurology
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Perron Institute for Neurological and Translational Science
• Austria
  • Graz, Austria, 8036
    • Medizinische Universität Graz; Universitätsklinik für Neurologie
  • Innsbruck, Austria, 6020
    • Uniklinik fuer Neurologie, Medizinische Universitaet Innsbruck; Department fuer Neurologie
  • Salzburg, Austria, 5020
    • Christian-Doppler-Klinik - Universitätsklinikum; Universitätskliniik für Neurologie
  • Wien, Austria, 1090
    • Medizinische Universität Wien; Univ.Klinik fuer Neurologie
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint Jan
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • La Louvière, Belgium, 7100
    • Chu Tivoli
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
  • Overpelt, Belgium, 3900
    • Revalidatie en MS Centrum
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 31270-901
      • Hospital das Clinicas - UFMG
  • PR
    • Curitiba, PR, Brazil, 81210-310
      • Instituto de Neurologia de Curitiba
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
      • Hospital Sao Lucas - PUCRS
  • SP
    • Sao Paulo, SP, Brazil, 05403-010
      • Hospital das Clinicas - FMUSP
• Bulgaria
  • Sofia, Bulgaria, 1113
    • Shat Np Sveti Naum; 3Rd Clinic of Neurology
  • Sofia, Bulgaria, 1431
    • UMHAT Alexandrovska, EAD; Neurology
  • Sofia, Bulgaria, 1309
    • Multiprofile Hosp. for Active Treatment;National Cardiology Hosp.
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 1Z3
      • UBC Hospital; Div of Neurology, Dept of Medicine
  • Ontario
    • London, Ontario, Canada, N6A 5A5
      • London Health Sciences Centre Uni Campus
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Science Centre
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 1W2
      • Clinique NeuroOutaouais
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Recherche Sepmus Inc.
    • Montreal, Quebec, Canada, H3A 2B4
      • Montreal Neurological Institute and Hospital
• Croatia
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb
• Denmark
  • Aalborg, Denmark, 9000
    • Aalborg Universitetshospital; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb.
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken
  • Glostrup, Denmark, 2600
    • Rigshospitalet; Neurologisk Klinik Glostrup
• France
  • Besançon, France, 25030
    • CHU de Besancon Hopital Jean Minjoz; Service de Neurologie
  • Bordeaux, France, 33076
    • Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
  • Bron, France, 69677
    • Hopital Pierre Wertheimer; Neurologie D
  • Caen, France, 14033
    • CHU de Caen Hopital Cote de Nacre
  • Clermont Ferrand, France, 63003
    • CHU Hopital Gabriel Montpied; Service de Neurologie
  • Gonesse, France, 95503
    • CH de Gonesse; Neurologie
  • La Tronche, France, 38700
    • CHU de Grenoble; Neurologie
  • Montpellier, France, 34295
    • Hopital Gui de Chauliac; Neurologie
  • Nancy, France, 54035
    • Hopital Central - CHU de Nancy; Service de Neurologie
  • Nantes, France, 44805
    • Hôpital Guillaume et René Laënnec; Service Neurologie
  • Nice, France, 06002
    • Hôpital Pasteur; Service de Neurologie
  • Nimes, France, 30900
    • CHU de Nîmes Hopital Caremeau; Service de Neurologie
  • Poissy, France, 78300
    • Hôpital de Poissy; Service neurologie
  • Rennes, France, 35033
    • Centre Hospitalier Universitaire de Rennes
  • Rouen, France, 76031
    • CHU de Rouen Hopital; Service de Neurologie
  • Strasbourg, France, 67098
    • CHU de Strasbourg
  • Suresnes, France, 92151
    • Hopital Foch; Neurologie
  • Toulon, France, 83041
    • HIA de Toulon hôpital militaire; Neurologie
  • Toulouse, France, 31059
    • CHU toulouse - Hôpital Purpan; Departement de Neurologie
  • Tours, France, 37000
    • CHRU - Hôpital Bretonneau; Neurologie
• Germany
  • Barsinghausen, Germany, 30890
    • Praxis Dr.med. Sylvia Menck, Fachärztin für Neurologie und Psychiatrie
  • Berlin, Germany, 13347
    • Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
  • Bochum, Germany, 44791
    • St. Josef-Hospital, Klinik für Neurologie
  • Böblingen, Germany, 71034
    • Studienzentrum Dr. Bischof GmbH
  • Dresden, Germany, 01307
    • Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
  • Düsseldorf, Germany, 40225
    • Universitätsklinikum Düsseldorf; Klinik für Neurologie
  • Erbach/Odenwald, Germany, 64711
    • NeuroCentrum Odenwald; Dres. Reifschneider, Unsorg, Ries, Schumann, Hoffmann, Knoblich
  • Essen, Germany, 45147
    • Universitätsklinikum Essen (AöR); Klinik für Neurologie
  • Hamburg, Germany, 22179
    • MultipEL Studies - Institut für klinische Studien
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Kassel, Germany, 34121
    • Neurologische Gemeinschaftspraxis Kassel und Vellmar, Ch. Lassek, Dres. Ammerbach, Fetzer, M. Fische
  • Kiel, Germany, 24105
    • Uniklinik Schleswig-Holstein; Neuroimmunologie, Institut für Klinische Chemie + Klinik f. Neurologie
  • Marburg, Germany, 35043
    • Universitaetsklinikum Marburg; Klinik fuer Neurologie
  • München, Germany, 81675
    • Klinikum rechts der Isar der TU Muenchen; Neurologische Klinik und Poliklinik im Neuro-Kopf-Zentrum
  • Münster, Germany, 48149
    • Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie
  • Neuburg, Germany, 86633
    • Praxis Dr. med. Bergmann
  • Seesen, Germany, 38723
    • Asklepios Kliniken Schildautal Seesen; Klinik für Neurologie
  • Tübingen, Germany, 72076
    • Universitätsklinikum Tübingen, Zentrum für Neurologie
• Hungary
  • Budapest, Hungary, 1083
    • Semmelweis Egyetem AOK; Neurologiai Klinika
  • Budapest, Hungary, 1204
    • Jahn Ferenc Dél-Pesti Kórház
  • Budapest, Hungary, 1145
    • Budapesti Uzsoki Utcai Korhaz
  • Esztergom, Hungary, 2500
    • VALEOMED Diagnosztikai Központ
  • Szeged, Hungary, 6725
    • Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ; Neurológiai Klinika
• Italy
  • Calabria
    • Catanzaro, Calabria, Italy, 88100
      • A.O.U. Mater Domin; U.O. NEUROLOGIA
  • Campania
    • Napoli, Campania, Italy, 80131
      • A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche
    • Napoli, Campania, Italy, 80131
      • Università degli Studi della Campania Luigi Vanvitelli; Dip. Ass. Integrato Med Int-II Clinica Neur
  • Friuli-Venezia Giulia
    • Trieste, Friuli-Venezia Giulia, Italy, 34149
      • Ospedale Cattinara; Amb Studio Sclerosi Multipla, Clinica Neurlogica
  • Lazio
    • Roma, Lazio, Italy, 00133
      • Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
    • Roma, Lazio, Italy, 00189
      • Azienda Ospedaliera Sant'Andrea; UOC Neurologia
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Irccs A.O.U.San Martino Ist; Dinogmi
  • Lombardia
    • Milano, Lombardia, Italy, 20133
      • Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari
    • Milano, Lombardia, Italy, 20132
      • IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla
    • Montichiari, Lombardia, Italy, 25018
      • Ospedale Civile di Montichiari; Centro Sclerosi Multipla
  • Molise
    • Pozzilli, Molise, Italy, 86077
      • IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla
  • Sicilia
    • Catania, Sicilia, Italy, 95123
      • AOU Policlinico V. Emanuele - P.O G. Rodolico; Clinica Neurologica, Centro Sclerosi Multipla
    • Palermo, Sicilia, Italy, 90146
      • AO Ospedali Riuniti Villa Sofia-Cervello;PO Villa Sofia - UO Neurologia - U.O.S. Neuroimmunologia
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • AOU Careggi; Neurologia 1-Dip. Neuroscienze Psicologia Area Farmaco Salute del Bambino(NEUROFARBA)
    • Grosseto, Toscana, Italy, 58100
      • Ospedale Misericordia USL9 di Grosseto; U.O. Neurologia
    • Siena, Toscana, Italy, 53100
      • Ospedale Le Scotte; Clinica Neurologica e Malattie Neurometaboliche
• Kuwait
  • Kuwait, Kuwait, 10002
    • Ibn Sina Hospital; Neurology Department
• Lebanon
  • Beirut, Lebanon, 1107 2020
    • American University of Beirut - Medical Center
• Mexico
  • Ciudad de México, Mexico, 14050
    • Unidad de investigacion en salud (UIS); Neurociencias
  • Sinaloa
    • Culiacán, Sinaloa, Mexico, 80020
      • Neurociencias Estudios Clinicos S.C.
  • Tlaxcala
    • Mexico, Tlaxcala, Mexico, 06726
      • Hospital General De Mexico
• Netherlands
  • 'S Hertogenbosch, Netherlands, 5223 GZ
    • Jeroen Bosch Ziekenhuis
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum; Afdeling Neurologie
  • Gouda, Netherlands, 2803 HH
    • Groene Hart Ziekenhuis
  • Sittard-Geleen, Netherlands, 6162 BG
    • Zuyderland Medisch Centrum - Sittard Geleen
• Norway
  • Lørenskog, Norway, 1478
    • Akershus universitetssykehus HF; Nevroklinikken S203
  • Stavanger, Norway, 4011
    • Stavanger Universitetssykehus, Helse Stavanger HF
• Poland
  • Bydgoszcz, Poland, 85-796
    • Neurocentrum Bydgoszcz sp. z o.o
  • Gdansk, Poland, 80-803
    • COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny
  • Katowice, Poland, 40-568
    • CARe Clinic
  • Krakow, Poland, 31-637
    • Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o.
  • Lodz, Poland, 90-324
    • Centrum Neurologii Krzysztof Selmaj
  • Lublin, Poland, 20-410
    • Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak.
  • Warszawa, Poland, 02-097
    • Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
  • Warszawa, Poland, 02-957
    • Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
• Portugal
  • Almada, Portugal, 2801-951
    • Hospital Garcia de Orta; Servico de Neurologia
  • Braga, Portugal, 4710-243
    • Hospital de Braga; Servico de Neurologia
  • Coimbra, Portugal, 3000-075
    • HUC; Servico de Neurologia
  • Loures, Portugal, 2674-514
    • Hospital Beatriz Angelo; Servico de Neurologia
  • Porto, Portugal, 4099-001
    • Hospital Geral de Santo Antonio; Servico de Neurologia
• Romania
  • Bucharest, Romania, 11172
    • Spitalul Universitar de Urgenta Bucuresti
  • Sibiu, Romania, 550245
    • Spitalul Clinic Judetean Sibiu
  • Targu-Mures, Romania, 540136
    • Spitalul Clinic Judetean de Urgenta Mures
• Slovakia
  • Bratislava, Slovakia, 826 06
    • Univerzitna nemocnica Bratislava - Nemocnica Ruzinov; Neurologicka klinika SZU a UNB
  • Bratislava, Slovakia, 813 69
    • Univerzitna nemocnica Bratislava, Nemocnica Staré Mesto; I. Neurologická klinika SZU a UNB
  • Nitra, Slovakia, 949 11
    • GB NeuroPRAKTIK, s.r.o
  • Trnava, Slovakia, 917 75
    • Fakultna nemocnica Trnava
• Slovenia
  • Ljubljana, Slovenia, 1000
    • University Medical Centre; Neurology
  • Maribor, Slovenia, 2000
    • University Medical Centre Maribor
• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante; Servicio de Neurología
  • Barcelona, Spain, 08003
    • Hospital del Mar; Servicio de Neurologia
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron; Servicio de Neurología
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología
  • Murcia, Spain, 30008
    • Hospital General Universitario Morales Meseguer; Servicio de Neurología
  • Tenerife
    • Santa Cruz De Tenerife, Tenerife, Spain, 38010
      • Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia
  • Vizcaya
    • Barakaldo, Vizcaya, Spain, 48903
      • Hospital de Cruces; Servicio de Neurologia
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska Sjukhuset; Neurology
  • Karlstad, Sweden, 651 85
    • Centralsjukhuset; Neurologi och rehabiliteringskliniken
  • Stockholm, Sweden, 113 41
    • Centrum för neurologi
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel; Neurologie
  • Bern, Switzerland, 3010
    • Inselspital Bern Medizin Neurologie; Neurologische Poliklinik
  • Lugano, Switzerland, 6903
    • Ospedale Regionale di Lugano - Civico; Neurologia
  • Luzern, Switzerland, 6004
    • Luzerner Kantonsspital Luzern Medizin Neurologie
  • St. Gallen, Switzerland, 9007
    • Kantonsspital; Neurologische Klinik
• Turkey
  • Ankara, Turkey, 06100
    • Hacettepe University Medical Faculty; Neurology
  • Ankara, Turkey, 06500
    • Gazi University Medical Faculty; Departmant of Norology
  • Hatay, Turkey, 31001
    • Mustafa Kemal Ataturk UTF; Department of norology
  • Istanbul, Turkey, 34098
    • Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali
  • Istanbul, Turkey, 34394
    • Istanbul Bilim Universty Medical Fac.
  • Istanbul, Turkey, 34093
    • Istanbul University Istanbul Medical Faculty; Neurology
  • Istanbul, Turkey, 42131
    • Selcuk University Medical Faculty; Norology department
  • Samsun, Turkey, 55139
    • Ondokuz Mayis Univ. Med. Fac.; Neurology
  • Trabzon, Turkey, 61080
    • Karadeniz Tecnical Uni. Med. Fac.; Neurology
• United Kingdom
  • Cambridge, United Kingdom, CB2 0QQ
    • Cambridge University Hospitals NHS Foundation Trust
  • Glasgow, United Kingdom, G51 4TF
    • Queen Elizabeth University Hospital
  • London, United Kingdom, SE5 9RS
    • King's College Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, NW3 2QS
    • Royal Free Hospital
  • London, United Kingdom, WC1N 3BG
    • National Hospital for Neurology and Neurosurgery,; MRC Centre for Neuromuscular Diseases
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Royal Victoria Infirmary
  • Plymouth, United Kingdom, PL6 8BT
    • Derriford Hospital
  • Salford, United Kingdom, M6 8HD
    • Salford Royal NHS Foundation Trust
  • Swansea, United Kingdom, SA6 6NL
    • Abertawe and Bro Morgannwg NHS Trust; Clinical Researdh Institute
• United States
  • California
    • Irvine, California, United States, 92697
      • University of California Irvine
    • Sunnyvale, California, United States, 94086
      • Palo Alto Medical Foundation Research Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurology of Colorado, LLC
  • Connecticut
    • Stamford, Connecticut, United States, 06905
      • KI Health Partners, LLC; New England Institute for Clinical Research
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University Medical Center
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida - Bradenton
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Shepherd Center Inc.
  • Kansas
    • Overland Park, Kansas, United States, 66212
      • College Park Family Care Ctr
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70810
      • The Neuromedical Center
  • Maine
    • Scarborough, Maine, United States, 04074
      • Maine Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center; Department of Neurology
  • Massachusetts
    • Foxboro, Massachusetts, United States, 02035
      • Neurology Center of New England
    • Wellesley, Massachusetts, United States, 02481
      • Dragonfly Research, LLC
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo; Center for Brain Research
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Plainview, New York, United States, 11803
      • Island Neurological Associates, P.C.
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • Neurology Associates PA
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Health Sciences
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40
    • Dayton, Ohio, United States, 45417
      • Neurology Specialists, Inc
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Bedford, Texas, United States, 76021
      • Kane Hall Barry Neurology
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a definite diagnosis of RRMS, as per the revised McDonald 2010 criteria
• Have a length of disease duration, from first documented clinical attack consistent with MS disease of less than or equal to (</=) 3 years
• Within the last 12 months one or more clinically reported relapse(s) or one or more signs of MRI activity
• EDSS of 0.0 to 3.5 inclusive, at screening
• An agreement to use an acceptable birth control method for women of childbearing potential, during the treatment period and for at least 6 months or longer after the last dose of study drug

Exclusion Criteria:

• Secondary progressive multiple sclerosis or history of primary progressive or progressive relapsing MS
• Inability to complete an MRI
• Known presence of other neurological disorders

Exclusions Related to General Health:

• Pregnancy or lactation
• Participants intending to become pregnant during the study or within 6 months after the last dose of the study drug
• Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• History or currently active primary or secondary immunodeficiency
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Significant or uncontrolled somatic disease or any other significant disease that may preclude participant from participating in the study
• Congestive heart failure (New York Heart Association III or IV functional severity)
• Known active bacterial, viral, fungal, mycobacterial infection or other infection, (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to screening or oral antibiotics 2 weeks prior to screening
• History of malignancy, major opportunistic infections, alcohol or drug abuse, recurrent or chronic infection, and/or coagulation disorders

Exclusions Related to Medications:

• Received any prior approved disease modifying treatment (DMT) with a label for MS, for example, interferons, glatiramer acetate, natalizumab, alemtuzumab, daclizumab, fingolimod, teiflunomide and dimethylfumarate
• Receipt of a live vaccine or attenuated live vaccine within 6 weeks prior to the baseline visit
• Previous treatment with B-cell targeted therapies (i.e., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
• Any previous treatment with immunosuppressants/ immunomodulators/ antineoplastic therapies (cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, cladribine, mitoxantrone, laquinimod, total body irradiation, or bone marrow transplantation)
• Treatment with investigational DMT
• Treatment with fampridine/dalfamipridine unless on stable dose for >/=30 days prior to screening

Exclusion related to Shorter Infusion Substudy:

- Any previous serious IRRs experienced with ocrelizumab treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ocrelizumab; Ocrelizumab will be administered intravenously (IV) as two 300-milligram (mg) infusions (infusion length=2.5 hours) on Days 1 and 15, followed by one 600-mg infusion dose every 24 weeks (+/- 14 days) for a maximum of 8 doses throughout the 192 weeks treatment period.	Drug: Ocrelizumab; Ocrelizumab will be administered via IV infusion as specified throughout the treatment period.
Active Comparator: Substudy Group 1; At week 24 of the main study, eligible participants will be randomized to receive 600 mg ocrelizumab infused over approximately 3.5 hours every 24 weeks for the remainder of the study duration	Drug: Ocrelizumab; Ocrelizumab will be administered via IV infusion as specified throughout the treatment period.
Experimental: Substudy Group 2; At week 24 of the main study, eligible participants will be randomized to receive 600 mg ocrelizumab infused over approximately 2 hours followed by sodium chloride given as a slow infusion over the remaining 1.5 hours to mimic the standard-length infusion (3.5 hour) every 24 weeks for the remainder of the study duration	Drug: Ocrelizumab; Ocrelizumab will be administered via IV infusion as specified throughout the treatment period.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in EDSS Score at Week 96		Baseline, Week 96
Mean Change From Baseline in EDSS Score at Week 120		Baseline, Week 120
Mean Change From Baseline in EDSS Score at Week 144		Baseline, Week 144
Mean Change From Baseline in EDSS Score at Week 168		Baseline, Week 168
Mean Change From Baseline in EDSS Score at Week 192		Baseline, Week 192
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks and 48 Weeks as Measured Using Expanded Disability Status Scale (EDSS)	The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits for a minimum of 24 weeks/48 weeks.	Baseline up to 4 years
Percentage of Participants With 24-Week and 48-Week Confirmed Disability Improvement (CDI) During the Year 1 Treatment Period, as Measured Using EDSS	CDI is defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).	At Weeks 24 and 48 during Year 1
Percentage of Participants Event-Free for CDP Sustained for at Least 24 and 48 Weeks at Year 1, as Measured Using EDSS	The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.	Year 1 (Weeks 24 and 48)
Percentage of Participants With 24-Week and 48-Week CDI During the Year 2 Treatment Period, as Measured Using EDSS	CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24/48 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).	At Weeks 48, 72 and 96 during Year 2
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 2, as Measured Using EDSS	The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.	Year 2 (Weeks 72 and 96)
Percentage of Participants With 24-Week and 48-Week CDI at Year 4, as Measured Using EDSS	CDI is defined as an improvement of 1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological worsening (measured only participants with a baseline EDSS of ≥2.0). EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).	At Weeks 144, 168 and 192 during Year 4
Percentage of Participants Event-free for CDP Sustained for at Least 24 and 48 Weeks at Year 4, as Measured Using EDSS	The EDSS-Expanded Disability Status Scale is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Disability progression as measured by EDSS is defined as ≥1 point increase in EDSS score from a baseline EDSS score of 1-5 inclusive, a 0.5-increase from a baseline EDSS score higher than 5 and a 1.5-increase from a baseline EDSS score from 0 to 1 exclusive. Disability progression was considered confirmed if a sustained change in EDSS for a minimum of 24 weeks (-2 weeks) from the initial progression event was seen i.e. the change in EDSS must have been sustained at all available visits (during Year 1) for a minimum of 24 weeks/48 weeks. Percentage of participants who did not have CPD sustained for 24 and 48 weeks are reported here.	Year 4 (Weeks 168 and 192)
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS		Year 1 (Week 48)
Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS		Year 2 (Week 96)
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 3, As Measured Using EDSS		Year 3
Percentage of Participants Who Have Improved, Stable, or Worsened Disability at Year 4, As Measured Using EDSS		Year 4
Mean Change From Baseline in EDSS Score at Week 24		From Baseline to Week 24
Mean Change From Baseline in EDSS Score at Week 48		From Baseline to Week 48
Mean Change From Baseline in EDSS Score at Week 72		From Baseline to Week 72
Percentage of Participants Without Protocol-Defined Event of Disease Activity	Protocol-defined event of disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis [MS], as determined using EDSS/Functional Systems Score [FSS] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8 (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan.	Baseline up to 4 years
Percentage of Participants Without Relapse	Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.	Baseline up to 4 years
Annualized Relapse Rate	Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment. The adjusted annualized relapse rate is reported which is: Adjusted by age at disease diagnosis, Baseline EDSS, Presence of T1 Gd-enhanced lesion at screening and Presence of relapses in the last year prior to enrollment. Log-transformed exposure time is included as an offset variable. The report contains data up to week 192 of the treatment period of each individual participant.	Baseline up to 4 years
Sub Study: Number of Participants With IRRs Occurring During or Within 24 Hours Following the First Infusion After Randomization to the Shorter Infusion Substudy		Week 24 through Week 144

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD)	NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gd-enhancing lesion. CDP will be assessed using EDSS. Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.	Weeks 96, 192
Percentage of Participants Who Are Relapse Free	Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.	Week 192
Percentage of Participants With No Evidence of Protocol Defined Disease Activity	Protocol-defined disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis [MS], as determined using EDSS/Functional Systems Score [FSS] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8. (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan. Event-free rate	Weeks 96, 144, 192
Percentage of Participants Without Protocol-defined Event of Evidence of Progression (NEP)	NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20 percent [%] increase from baseline in timed 25 Foot Walk Test [T25FWT]; 20% increase from baseline in timed 9 hole peg test [9HPT]). CDP will be assessed using EDSS.	Weeks 96, 192
Secondary: Change From Baseline in Multiple Sclerosis Functional Composite Score (MSFC) Total	MSFC combines the following: Timed 25 Foot Walk Test [T25FWT] for leg function &ambulation measured in seconds (sec). The longer it takes to walk, higher the score indicating deterioration; 9 Hole Peg Test [9HPT] for arm & handf unction measured in sec. Higher score=more time taken to complete test indicating deterioration. Paced Auditory Serial Addition Test [PASAT] for cognitive function (score range: 0-60, higher score=better cognitive processing speed). MSFC composite={[Average(1/9-HPT)-Baseline Mean(1/9-HPT)/Baseline Std Dev(1/9-HPT)]+[-(Average T25FWT-Baseline Mean T25FWT)/Baseline Std-Dev T25FWT]+[(PASAT-3-BaselineMean PASAT-3)/Baseline Std Dev PASAT-3]}/ 3.0. MSFC is based on the concept that scores for these 3 dimensions are combined to create a single score to detect change over time in a group of MS patients. Higher composite score=better overall function. Lower score=worse overall function. Higher mean change in total MSFC score=functional improvement at cohort level.	Weeks 24, 48, 72, 96, 120, 144, 168, 192
Change From Baseline in MSFC Composite Timed 25 Foot Walk Test (T25FW) Score.	The change in the mean score of T25FW is reported below. The time taken to walk 25 feet, typically measured in seconds. The longer it takes to walk, the higher score, which indicates deterioration. Lower times indicate better performance and greater mobility. Higher times indicate worse performance and greater impairment. Subsequently, the lower the mean change in the score over time, the better performance.	Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192
Change From Baseline in MSFC Composite 9 Hole Peg Test (9HPT) Score	The mean change in 9 Hole Peg Test (9HPT)-score is reported. Participants are instructed to place pegs one by one into each of nine holes arranged in a board stabilized with a plastic nonslip sheet on a solid table, and then to remove these pegs from the holes. Both the dominant and non-dominant hands are tested twice (two consecutive trials for each hand). The participants are required to complete two successful trials for each hand. The amount of time (in seconds) required to place and remove all nine pegs is recorded for each trial. The number of seconds it takes to complete the test, the higher raw scores, which indicates deterioration. The lower mean change in the score over time, the better the performance.	Weeks 24, 48, 72, 96, 120, 144, 168, 192
Change From Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score	Mean change in the Paced Auditory Serial Addition Test [PASAT] score is reported. PASAT measures cognitive function. A total of 60 single digit numbers are presented by an audiotape/CD-rom at a constant rate in every 3 seconds (PASAT-3). Participants are required to add each new number to the one immediately before it. Due to the relative complexity of this test, a practice trial with a set of 10 numbers should be performed before the original test. Participants are allowed up to 3 practice trials. Two sets of numbers (forms A & B) are developed to be used alternatively in every visit to minimize memorizing. The number of correct answers is recorded. The PASAT score ranges from 0 to 60, with higher values representing a better outcome in cognitive processing speed. Subsequently, higher values in mean changes from baseline over the study time indicate improvement in cognitive function.	Weeks 24, 48, 72, 96, 120, 144, 168, 192
Change From Baseline in Cognitive Performance as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) - Symbol Digits Modalities Test (SDMT)	BICAMS is assessing cognitive processing speed and verbal and visual memory. SDMT assesses processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 second time span. The higher the results, the better processing speed/working memory.	Baseline, Weeks 48, 96, 144, 192
Change From Baseline in Cognitive Performance as Measured by BICAMS -California Verbal Learning Test-II (CVLT-II)	BICAMS assesses cognitive processing speed and verbal and visual memory. The CLVT-II is an assessment of verbal learning and memory which measures recall and recognition scores, encoding strategies, learning rates and error types. A list learning task with 16 words from 4 semantic categories are read over a series of 5 list presentations. Recall is assessed after learning and at a 20-minute delay. The maximum possible score is 80 and a minimum is 0. A higher score indicated better recall.	Baseline, Weeks 48, 96, 144, 192
Change From Baseline in Cognitive Performance as Measured by BICAMS - Brief Visuospatial Memory Test-Revised (BVMT-R)	BICAMS assesses cognitive processing speed and verbal and visual memory. BVMT-R assesses visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.	Baseline, Weeks 48, 96, 144, 192
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI	Number of Lesions are categorized as followed: 1, 2, 3, >1, >3	Weeks 24, 48, 96, 144, 192
Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI	Number of Lesions are categorized as followed: 1, 2, 3, >1	Baseline, Weeks 24, 48, 96, 144, 192
Change From Baseline in Total T1 Hypointense Lesion Volume as Detected by Brain MRI		Baseline, Weeks 48, 96, 144, 192
Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI	Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI was measured for its volumes.	Baseline, Weeks 8, 24, 48, 96, 144, 192
Change From Baseline in Brain Volume as Detected by Brain MRI	Percentage change from Normalized brain volume in cm3 (cubic centimeter)values are reported	From Baseline to Weeks 24, 48, 96, 144, 192
Percentage of Participants Without Treatment Discontinuation		Baseline up to 4 years
Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score	WPAI scale measures impact of health problems on work productivity and regular activities: Absenteeism (Work Time Missed) measuring % of work time missed due to health issues; Presenteeism:Calculated as the percentage of impairment while working due to health problems. Overall Work Impairment:Calculated by combining absenteeism and presenteeism using the formula:Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism Overall Work Impairment=Absenteeism+(1-Absenteeism)×Presenteeism This formula accounts for both the time missed and the reduced productivity while at work. Activity Impairment: Calculated as the percentage of impairment in regular activities outside of work. Range: Each component is scored as 0%-100%). Higher % indicate greater impairment and worse outcomes.	Baseline, Weeks 24, 48, 96, 120, 144, 192
SymptoMScreen Composite Score	The SMSS consists of 12 items which are assessed on a seven-point Likert scale that ranges from 0 (not at all affected) to 6 (total limitation) [7]. The total score ranges from 0 to 72, with higher scores indicating more severe symptom endorsement.	Baseline, Weeks 24, 48, 96, 144, 192
Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score	The 29-item Multiple Sclerosis Impact Scale (MSIS-29) is a questionnaire to examine the impact of multiple sclerosis (MS) on physical and psychological functioning from a patient's perspective, which includes 29 items self-reported measures associated with a physical scale and 9 items with a psychological scale. MSIS-29 scales are generated by summing items and it's ranging from 29-145'. The higher total MSIS-29 scores indicate a greater degree of disability. The mean change in MSIS-29 scores from baseline is reported. The decreasing values in the mean change from baseline indicate functional improvement from patients' perspective	Baseline, Weeks 24, 48, 96, 144, 192
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)		Baseline up to 4 years
Substudy: Number of Participants With IRR Overall and by Dose at Randomization		From Week 24 to Week 144
Substudy: Severity of IRRs	The number of participants with IRRs by most extreme intensity were reported (Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 =life-threatening, grade 5 = fatal). Multiple IRRs in one participant are counted only once at the most extreme (highest) intensity observed.	From Week 24 to Week 144
Substudy: Number of IRR Symptoms		From Week 24 to Week 144
Substudy: IRRs Leading to Treatment Discontinuation		From Week 24 to Week 144

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• Hartung HP; ENSEMBLE Steering Committee members and study investigators. Ocrelizumab shorter infusion: Primary results from the ENSEMBLE PLUS substudy in patients with MS. Neurol Neuroimmunol Neuroinflamm. 2020 Jun 4;7(5):e807. doi: 10.1212/NXI.0000000000000807. Print 2020 Sep.

Study record dates

Study Major Dates

• Study Start (Actual): March 24, 2017
• Primary Completion (Actual): April 27, 2023
• Study Completion (Actual): April 27, 2023

Study Registration Dates

• First Submitted: March 16, 2017
• First Submitted That Met QC Criteria: March 16, 2017
• First Posted (Actual): March 21, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 20, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Immunologic Factors; Physiological Effects of Drugs; Ocrelizumab
• Other Study ID Numbers: MA30143; 2016-002937-31 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No